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Noroviruses (NoVs) are a major cause of epidemic gastroenteritis in children and adults. Several pieces of evidence suggest that viruses genetically and antigenically closely related to human NoVs might infect animals, raising public health concerns about potential cross-species transmission. The natural susceptibility of non-human primates (NPHs) to human NoV infections has already been reported, but a limited amount of data is currently available. In order to start filling this gap, we screened a total of 86 serum samples of seven different species of NPHs housed at the Zoological Garden (Bioparco) of Rome (Italy), collected between 2001 and 2017, using an enzyme-linked immunosorbent assay (ELISA) based on virus-like particles (VLPs) of human GII.4 and GIV.1 NoVs. Antibodies specific for both genotypes were detected with an overall prevalence of 32.6%. In detail, IgG antibodies against GII.4 NoVs were found in 18 Japanese macaques (29.0%, 18/62), a mandrill (10.0%, 1/10), a white-crowned mangabey (16.6%, 1/6) and in an orangutan (33.3%, 1/3). Twelve macaques (19.3%, 12/62), five mandrills (50.0%, 5/10), two chimpanzees (100%, 2/2) and a white-crowned mangabey (16.6%, 1/6) showed antibodies for GIV.1 NoVs. The findings of this study confirm the natural susceptibility of captive NHPs to GII NoV infections. In addition, IgG antibodies against GIV.1 were detected, suggesting that NHPs are exposed to GIV NoVs or to antigenically related NoV strains.

Human Norovirus (HuNoV) is the leading cause of epidemic gastroenteritis cases worldwide. HuNoV is a major public health problem resulting in 677–700 million cases and >200,000 deaths annually in addition to a yearly economic burden of >$64 billion. Noroviruses are single-stranded RNA viruses of the family Caliciviridae. Based on the viral capsid protein, noroviruses are classified into ten genogroups (GI-GX) with norovirus genogroup II genotype 4 (GII.4) being the predominant strain causing human illness. While the latter is self-limiting among immunocompetent individuals, noroviruses lead to hospitalization among children less than 5 years old and elderly. Currently, supportive therapy involving reversal of dehydration and electrolyte deficiency is the main treatment for norovirus-associated gastroenteritis. A vaccine is urgently needed to prevent the impact of norovirus-associated acute gastroenteritis globally. This chapter presents an up-to-date overview of the available data on the development of norovirus vaccine obtained from challenge, preclinical (animal) and clinical studies as well as the challenges and the obstacles facing the development of a preventive and broadly protective vaccine.

Rotaviruses and adenoviruses conjointly form the leading cause of epidemic gastroenteritis in developed and developing countries. The prevalence of this array of human viral pathogens in under five years children of Dustin-ma Local Government Area of Katsina State, North-west Nigeria was investigated on diarrheal stool samples of 152 patients of acute viral gastroenteritis by Reverse Transcription Polymerase Chain Reaction (RT-PCR) as approved by the state committee on ethics after parental agreement. Analyses revealed prevalence of 54% (35/65) and 46% (30/65) for rotaviruses and adenoviruses respectively in 2013 and then 62.2% (51/82) for rotaviruses followed by 37.8% (31/82) for adenoviruses in 2014 with a total of 87 rotavirus positive samples (57.24%) while 61 samples (40.13%) were adenovirus positive. Only 4 samples (3%) were infected by other diarrheal viral pathogens.

Purpose Norovirus is the leading cause of acute epidemic gastroenteritis among children under the age of 5 years and adults in the United States and in adults worldwide, accounting for an estimated 20% of episodes of acute gastroenteritis across all ages. No effective vaccine is presently available. This article provides an overview of the current state of norovirus vaccine development, emphasizing barriers and challenges in the development of an effective vaccine, correlates of protection used to assess vaccine efficacy, and the results of clinical trials of the major candidate vaccines. Methods We performed an unstructured literature review of published articles listed in PubMed in the field of norovirus vaccine development, with an emphasis on studies in humans. Findings Two candidate vaccines have reached clinical trials, and a number of other candidates are in the preclinical stages of development. Multivalent vaccination may be effective in inducing broadly neutralizing antibodies protective against challenge with novel and heterologous norovirus strains. Most identified correlates of protection have not been validated in large-scale challenge studies, nor have the degrees to which these correlates covary been assessed. Implications Immune correlates of protection against norovirus infection need to be further developed to facilitate additional studies of the tolerability and efficacy of candidate norovirus vaccines in humans.

Human norovirus is the major cause of non-bacterial epidemic gastroenteritis. Human norovirus binds to environmental solids via specific and non-specific interactions, and several specific receptors for human norovirus have been reported. Among them, histo-blood group antigens (HBGA) are the most studied specific receptor. Studies have identified the presence of HBGA-like substances in the extracellular polymeric substances (EPS) and lipopolysaccharides (LPS) of human enteric bacteria present in aquatic environments, gastrointestinal cells, gills, and palps of shellfish, and cell walls, leaves, and veins of lettuce. These HBGA-like substances also interact with human norovirus in a genotype-dependent manner. Specific interactions between human norovirus and environmental matrices can affect norovirus removal, infectivity, inactivation, persistence, and circulation. This review summarizes the current knowledge and future directions related to the specific interactions between human norovirus and HBGA-like substances in environmental matrices and their possible effects on the fate and circulation of human norovirus.

Norovirus (NoV) infection is the leading cause of epidemic gastroenteritis globally, and can lead to detrimental chronic infection in immunocompromised hosts. Despite its prevalence as a cause of diarrheal illness, the study of human NoVs (HNoVs) has historically been limited by a paucity of models. The use of murine NoV (MNoV) to interrogate mechanisms of host control of viral infection has facilitated the exploration of different genetic mouse models, revealing roles for both innate and adaptive immunity in viral regulation. MNoV studies have also recently identified important interactions between the commensal micro-biota and NoV with clear extensions to HNoVs. In this review, we discuss the most current understanding of how the host, the microbiome, and their interactions regulate NoV infections.

Background Norovirus (NoV) is the leading cause of epidemic gastroenteritis worldwide. The lack of a cell culture has significantly hampered the development of effective therapies against human NoV. Clinically approved nucleoside and non-nucleoside analogues have been used successfully against RNA viruses. Methods In this study, we evaluated the efficacy of four nucleoside analogues (2′-C-MeC, 2′-F-2′-C-MeC, β-D-N(4)-hydroxycytidine [NHC] and lamivudine) on Norwalk virus (NV) RNA levels and protein expression in NV replicon-harbouring cells (HG23 cells), and their efficacy in blocking murine norovirus (MNV) replication in RAW 264.7 cells. Results 2′-C-MeC and 2′-F-2′-C-MeC reduced MNV RNA levels and infectivity in RAW 264.7 cells in a concentration- and time-dependent manner. The median effective concentrations (EC50) of 2′-C-MeC and 2′-F-2′-C-MeC were 6.9 μM and 12.7 μM, respectively. 2′-C-MeC, 2′-F-2′-C-MeC and NHC reduced NV RNA levels and protein expression in HG23 cells. For the NV replicon, the EC50 of 2′-C-MeC (1.3 μM) was comparable to the antiviral activity of NHC (1.5 μM) and twofold more potent than 2′-F-2′-C-MeC (3.2 μM). The combination of 2′-C-MeC/ ribavirin resulted in modest synergistic activity, whereas NHC/ribavirin was antagonistic for NV replication in HG23 cells. Conclusions The antiviral activity of 2′-C-MeC against strains of two different NoV genogroups and the low EC50 suggest that this nucleoside analogue may be effective against the more prevalent GII NoVs. In the absence of a vaccine, antiviral agents could be an effective intervention to control the spread of human NoV in populations at a high risk for NoV disease.

Acute gastroenteritis represents a major cause of morbidity and mortality worldwide. Young children are affected most frequently, with three to 10 episodes of diarrhoea per subject per year, a rate that decreases to less than one episode annually for children over five years of age and adults. Usually, deaths are a result of dehydration, but malnutrition also plays an important role. Furthermore, malnutrition increases the incidence and severity of diarrhoea, as well as of other infections. The clinician encounters acute gastroenteritis in three settings. The first is sporadic gastroenteritis in infants, which is often caused by rotavirus. The second is epidemic gastroenteritis, which occurs either in semi-closed communities (e.g. families, institutions, on ships, at vacation spots) or as a result of classic food-borne or water borne pathogens. Most of these infections are caused by caliciviruses. The third is sporadic acute gastroenteritis of adults, which is most likely to be caused by caliciviruses, rotaviruses, astroviruses or adenoviruses.

Noroviruses are a common cause of both endemic and epidemic gastroenteritis. These highly infectious viruses usually cause self-limited disease, but chronic infections occur in highly immunocompromised patients and unusual manifestations are also being described in some populations. Histoblood-group antigen expression is now recognized as an important susceptibility factor for many norovirus strains, but a correlate of acquired immunity to infection or illness has not yet been identified. Currently, treatment and prevention strategies rely on non-specific measures. However, virus-like particles containing capsid antigens are undergoing evaluation as a vaccine candidate for illness prevention. This article reviews the biologic properties, epidemiology, clinical features, host susceptibility, diagnosis, and treatment and prevention of norovirus infection.

Noroviruses (NoVs) are a leading cause of sporadic and epidemic gastroenteritis across all age groups worldwide. The increasing recognition of the burden of disease caused by these viruses and their public health impact underscore the need for well tolerated and effective vaccines. In the absence of a completely permissive cell culture system, there is limited possibility of developing live-attenuated or killed NoV vaccines. Despite these challenges, many advances have been made in vaccine development in recent years. A number of vaccine candidates have been evaluated including the production of virus-like particles (VLPs) that are morphologically and antigenically identical to particles of the infectious virus. NoV VLPs appear to be attractive vaccine candidates, and the advances in the area of these vaccines are highly promising. This chapter summarizes data on immune correlates of protection against NoVs, preclinical and clinical studies with NoV candidate vaccines, and discusses the challenges remaining in the field of NoV vaccine development.

Human noroviruses are the major cause of nonbacterial, epidemic gastroenteritis worldwide ([19][1], [23][2], [33][3], [46][4]) and cause significant numbers of endemic cases, as well. One study from 1999 estimated that, in the United States alone, human noroviruses cause 23 million cases of

Despite the lack of a cell culture or animal model system, the past decade has seen tremendous advances in our understanding of NLV. Prior to 1990, the only nucleotide sequence information for caliciviruses was from viruses isolated from animals. There are now sequences available for more than 100 NLV isolates and more are rapidly accumulating. Such information is being used for development of new and more sensitive diagnostic assays. The CDC, under the National Food Safety Initiative and in cooperation with state and local governments, is working toward implementing routine surveillance and outbreak responses to limit or prevent widespread illness from the same identified source. Such increased surveillance and continued epidemiologic studies are necessary and critical to assess the risks and contain food-borne and water-borne outbreaks caused by the NLVs.

International audience; Noroviruses (NoVs) are the major cause of acute epidemic gastroenteritis in industrialized countries. Outbreak strains are predominantly genogroup II (GII) NoV, but genogroup I (GI) strains are regularly found in oyster related outbreaks. The prototype Norwalk virus (GI), has been shown to have high infectivity in a human challenge study. Whether other NoVs are equally infectious via natural exposure remains to be established. Human susceptibility to NoV is partly determined by the secretor status (Se+/-). Data from five published oyster related outbreaks were analyzed in a Bayesian framework. Infectivity estimates where high and consistent with NV(GI) infectivity, for both GII and GI strains. The median and CI95 probability of infection and illness, in Se+ subjects, associated with exposure to a mean of one single NoV genome copy were around 0.29[0.015–0.61] for GI and 0.4[0.04–0.61] for GII, and for illness 0.13 [0.007–0.39] for GI and 0.18 [0.017–0.42] for GII. Se- subjects were strongly protected against infection. The high infectivity estimates for Norwalk virus GI and GII, makes NoVs critical target for food safety regulations.

Sur la terre ferme, la sécurité est devenue un thème récurrent de la vie politique, des imaginaires voire de la réalité. Dans le monde de la croisière au contraire, la communication vend un univers idyllique. Or la réalité de la vie à bord du navire n’est pas faite que de bonheur, et les armateurs, les voyagistes, les équipages et les autorités administratives anticipent des situations qui mettent en péril les passagers. La gestion des épidémies ne se limite pas à la grippe H1N1, moment exceptionnel qui cache la réalité fréquente des épidémies de gastro-entérite. Le quotidien sécuritaire est aussi constitué par les risques plus traditionnels : le feu et le naufrage. La croisière également s’accompagne de viols et violences sur des croisiéristes, voire de disparitions de passagers. Ces trois dangers de la croisière font l’objet de mesures de santé publique, de définition de normes de sécurité internationales depuis 1914, et de mesures législatives récentes, puisque le dernier texte a été promulgué par le président Obama en juillet 2010. L’Europe montre un retard important dans l’organisation de cette politique, gage de développement de l’industrie de la croisière. On land, security has become a recurring theme in the political life of the imagination or reality. In the world of cruising the contrary, communication sells idyllic world. The reality of life on the ship is not made that happiness, and shipowners, operators, crews and administrative authorities anticipate situations that endanger passengers. Outbreak management is not limited to the H1N1 exceptional moment that hides the reality of frequent outbreaks of gastroenteritis. The daily safe is also constituted by the more traditional risks: fire and sinking. The cruise also accompanied by rape and violence on cruise or disappearances of passengers. These three dangers of the cruise are the subject of public health measures, definition of international safety standards since 1914, and recent legislation, since the final text was issued by President Obama in July 2010. Europe shows a significant delay in the organization of the political guarantee for the development of the cruise industry.

SUMMARYIn response to an alert due to epidemic gastroenteritis in children in a kindergarten, an outbreak investigation was carried out in a Portuguese municipality. The objectives were to establish an aetiological diagnosis, assess vaccine efficacy if possible, and to take corrective measures if necessary. The warden at the kindergarten was interviewed, and we visited the premises. The overall attack rate was 11·4% and most cases were mild. Stool samples from three symptomatic children were collected and screened for the presence of noroviruses, rotaviruses and adenoviruses. High vaccination coverage against rotaviruses was recorded in children aged

The noroviruses and sapoviruses belong to the Caliciviridae, a diverse family of positive-strand RNA viruses. This article describes the basic features of these enteric pathogens in relationship to other caliciviruses. The noroviruses are a major cause of epidemic gastroenteritis and outbreaks occur in settings such as communities, nursing homes, schools, hospitals, cruise ships, camps, social gatherings, families, and military personnel. Sapoviruses are most often associated with gastroenteritis in pediatric populations. The absence of efficient cell culture systems for the human calicivirus pathogens has been a major research obstacle for decades. However, recent advances in the development of molecular biologic tools and model systems have led to rapid advances in our understanding of these viruses.

Small round structured viruses (SRSV) are known to cause epidemic gastroenteritis in institutions and account for 54% of person to person outbreaks and 6% of foodborne outbreaks in England and Wales. Infection is commonly transmitted from person to person

Diarrheal illnesses in humans have been recognized since antiquity. Such illnesses continue to take a great toll of lives, with a disproportionately high mortality in infants and young children in developing countries. Bacteriologic and parasitologic advances made during the past century led to the discovery of the etiology of some of the diarrheal illnesses, but the etiology of the major portion remained unknown. It was assumed that viruses caused most of these illnesses because: (i) bacteria were recovered from only a small proportion of episodes, and (ii) bacteria-free filtrates were found to induce gastroenteritis in adult volunteer studies. However, an etiologic agent could not be recovered despite the “golden age” of virology in the 1950’s and 1960’s when tissue culture technology enabled the discovery of numerous cultivatable enteric viruses, none of which emerged as an important etiologic agent of gastroenteritis. The discoveries of the Norwalk virus in 1972, and of rotaviruses in 1973, both without the benefit of in vitro tissue culture systems, ushered in a new era in the study of the etiology of viral gastroenteritis. The Norwalk virus was found to be an important cause of non-bacterial epidemic gastroenteritis in adults and older children, and rotaviruses were shown to be the single most important etiologic agents of severe diarrheal illnesses of infants and young children in both developed and developing countries. With the major advances in the study of rotaviruses, there is a high degree of optimism that in the not-too-distant future, a rotavirus vaccine will be available. In addition, the recent molecular biologic advances in the study of the Norwalk and Norwalk-like viruses, now firmly established as caliviviruses, represent a major new horizon in the study of these viruses.

Noroviruses (NoVs) cause major epidemic gastroenteritis in humans. To obtain the molecular epidemiological information on gastroenteritis sporadic cases in Incheon city, Korea, we analyzed the nucleotide sequences of NoV strains detected during 2005~2007. We performed one step RT-PCR amplifying the open reading frame (ORF) 2 (capsid region) followed by semi-nested PCR from the stool samples from acute gastroenteritis patients from 2005 to 2007. Amplicons of the capsid region of norovirus strains were sequenced and analyzed using MegAlign in DNAstar software. Faecal samples were collected from 6,618 acute gastroenteritis patients during the study period. The incidence of NoV infection was about 10.7% (n=708) among patients with acute gastroenteritis and genotypes of the 320 positive samples were determined by sequence analysis. Sequence comparison of NoV strains revealed that 16 genotypes of GII NoV strains were circulated in Incheon city, from 2005 to 2007. Among norovirus strains, the most prevalent genotype GII/4 was most common 69.7% (223 strains), followed by GII/3 17.2% (55 strains), GII/12 4.4% (14 strains), GII/1 2.2% (7 strains), GII/5 1.6% (5 strains), GII/15 1.3% (4 strains) and 0.6% (2 strains) each of GII/9 and GII/16. The GII-3 strains were most frequently detected in Incheon, 2005. From the phylogenetic analysis of NoV strains, we detected 16 genotypes of GII NoV strains during 2005~2007 in Incheon. Our results suggest that various genotypes of human NoV strains in sporadic case of AGE were circulated in Incheon, Korea.

Considerable information has recently emerged regarding certain "groups" of novel viruses associated with gastroenteritis in humans. The viruses reviewed here are 20-35 nm in diameter and can be detected in the stools of acutely ill individuals with gastroenteritis. These viruses can be conveniently divided into four "groups": Norwalk-like agents, caliciviruses, astroviruses, and other small round viruses. The evidence for the etiologic association of these agents with gastroenteritis varies from agent to agent but is most extensive for the Norwalk-like agents, of which the Norwalk serotype is a major cause of epidemic gastroenteritis. Human caliciviruses appear to be relatively common causes of gastroenteritis in children, particularly in Japan and the United Kingdom. Astroviruses have been reported as occasional causes of gastroenteritis in children and adults in various parts of the world. The epidemiological significance of the other small round viruses is unknown. Because of the difficulty of cultivating these agents in vitro, biochemical and antigenic characterization of these agents is incomplete. An understanding of the pathogenesis of disease and of the roles of immune responses to infection is similarly at a primitive stage. The recent development of sensitive and efficient assays for detection of several of these agents and the reports that certain strains of human caliciviruses and astroviruses can be cultivated in vitro should facilitate characterization and epidemiological studies of these agents. Systematic, prospective epidemiological studies of these agents in well-defined populations of various age groups are sorely needed for definition of the relative importance of each agent in human disease. Such information is essential for the consideration of appropriate control measures.

Highlights • NoV was identified in the stools of diarrheal patients and controls in HCMC. • The locations of the NoV infections were GPS mapped. • A novel NoV GII.4-2010 (New Orleans) variant was detected. • The NoV GII.4-2010 demonstrated a significant spatiotemporal signal., Norovirus (NoV) is a major cause of epidemic gastroenteritis in industrialized countries, yet the epidemiological significance of NoV in industrializing countries remains poorly understood. The spatiotemporal distribution of NoV genotypes identified in 2054 enrolled children was investigated between May 2009 and December 2010, in Ho Chi Minh City (HCMC), Vietnam. A total of 315 NoV extracted from stool samples were genotyped and GPS mapped to their source. Genogroup II NoV, particularly GII.4, were predominant, and the GII.4 strains could be subgrouped into GII.4-2006b (Minerva) and GII.4-2010 (New Orleans) variants. There was no spatiotemporal structure among the endemic GII strains; yet a significant spatiotemporal signal corresponding with the novel introduction of GII.4-2010 variant was detected. These data show that NoV GII.4 variants are highly endemic in HCMC and describe a scenario of rapid NoV strain replacement occurring in HCMC in early 2010.

An outbreak of epidemic gastroenteritis associated with astrovirus, the first case reported in Japan, is described. Not only children (5-6 years of age), but also staff members of a kindergarten were affected. the virus particles detected in stools were 28-30 nm in diameter with a circular outline and had the characteristic star-like configuration which allowed identification as astrovirus. Significant immune responses to the virus were confirmed by immune electron microscopy. Out of 84 children, 43 (54.2%) were affected; the common symptoms were vomiting, abdominal pain, diarrhea, and fever. All the patients recovered completely within 48 hours. Occurrence of gastroenteritis due to contact with these patients was observed in 14 of 43 families.

Norovirus is the leading cause of epidemic gastroenteritis worldwide but the disease is usually self-limiting and generally only causes serious health problems in the young, elderly and immunocompromised. The authors report a case of bowel perforation in an elderly Caucasian lady with confirmed infection with Norovirus genogroup II and no other presumptive cause. To the authors' knowledge this is the first such case of bowel perforation due to Norovirus. Viral gastroenteritis should be considered in the list of differentials when no obvious cause of bowel perforation can be identified to minimise morbidity and mortality.